Anifrolumab (Monograph)

Brand name: Saphnelo
Drug class: IgG1 Monoclonal Antibodies

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

[Web]

Introduction

Immunosuppressive agent; type I interferon (IFN) receptor antagonist.

Uses for Anifrolumab

Systemic Lupus Erythematosus

Treatment of moderate to severe systemic lupus erythematosus (SLE) in adults; use in conjunction with other standard SLE therapies (e.g., corticosteroids, antimalarials, immunosuppressant agents).

Not evaluated and therefore not recommended in patients with severe active lupus nephritis or severe active CNS lupus.

The European Alliance of Associations for Rheumatology (EULAR) has provided guidelines on the management of SLE. In the 2019 EULAR guidelines, biologic agents are recommended in patients with an inadequate response to standard therapies; however, anifrolumab was not yet available when these guidelines were published.

Anifrolumab Dosage and Administration

General

Pretreatment Screening

Consider the potential risks and benefits before initiating anifrolumab in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection.
Consider the potential risks and benefits before initiating anifrolumab in patients with known risks factors for the development or recurrence of malignancy.
Update immunizations according to current immunization guidelines prior to initiating treatment with anifrolumab.

Patient Monitoring

Monitor for signs and symptoms of hypersensitivity and infusion-related reactions.
Monitor for signs and symptoms of infection during treatment.

Premedication and Prophylaxis

Consider premedication before infusions in patients with a history of hypersensitivity or infusion-related reactions.

Dispensing and Administration Precautions

Administer by healthcare providers prepared to manage hypersensitivity reactions and infusion-related reactions.

Administration

IV Administration

Administer by IV infusion over 30 minutes every 4 weeks.

Commercially available as an injection concentrate that must be diluted prior to IV administration.

Anifrolumab injection is preservative-free. Discard any unused portion left in the single-use vial after preparation.

If a planned infusion is missed, administer the missed infusion as soon as possible. Maintain a minimum interval of 14 days between infusions.

Do not administer other medications concomitantly via the same infusion line.

Interrupt the infusion if the patient develops any signs of adverse reactions, including infusion or hypersensitivity reactions.

Dilution

To prepare the diluted infusion solution, withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% sodium chloride injection bag using aseptic technique. Then, withdraw 2 mL (300 mg) of anifrolumab concentrate for injection from the single-use vial, and transfer to the 0.9% sodium chloride injection bag. Gently invert the bag of anifrolumab to mix; do not shake. Use the diluted solution immediately after preparation or store at room temperature for up to 4 hours or under refrigeration for up to 24 hours. If refrigerated, allow the diluted solution to come to room temperature prior to administration.

Rate of Administration

Administer the diluted solution via IV infusion over 30 minutes through an IV line containing a sterile, low-protein binding, in-line or add-on, 0.2–15-micron filter.

Dosage

Adults

Systemic Lupus Erythematosus

IV

300 mg by IV infusion every 4 weeks.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for Anifrolumab

Contraindications

History of anaphylaxis to anifrolumab.

Warnings/Precautions

Serious Infections

Serious, sometimes fatal, infections reported. Increased risk of respiratory infections and herpes zoster (including disseminated herpes zoster).

Consider risks and benefits of anifrolumab in patients with chronic infections, a history of recurrent infections, or known risk factors for infection. Avoid starting anifrolumab during an active infection until infection is treated or resolved. If an infection develops while on anifrolumab therapy or patient is not responsive to standard anti-infective treatment, seek medical treatment for the infection and monitor closely; consider interruption of therapy and closely monitor patient until resolution of the infection.

Hypersensitivity Reactions

Serious hypersensitivity reactions reported following anifrolumab administration; angioedema has also occurred.

Other hypersensitivity and infusion-related reactions have been reported. Consider premedication in patients with a history of these reactions prior to infusion of anifrolumab.

Administer anifrolumab only under the supervision of a healthcare provider prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If there is a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis), immediately stop administration and initiate appropriate therapy.

Malignancy

Immunosuppressants are associated with an increased risk of malignancies; specific risk for malignancy development in patients treated with anifrolumab not known.

Prior to initiating anifrolumab, consider benefits and risks in patients with known risk factors for the development or recurrence of malignancy. If malignancy develops during treatment, consider risk versus benefit of continuing anifrolumab.

Immunization

Update immunizations prior to initiation of anifrolumab in accordance with current immunization guidelines. Avoid use of live or live-attenuated vaccines during treatment.

Not Recommended for Concomitant Use with other Biologic Therapies

Not studied and not recommended for use in combination with other biologic agents, including B-cell targeted therapies.

Immunogenicity

Potential for immunogenicity. Anti-anifrolumab antibodies detected. Clinical relevance not known.

Specific Populations

Pregnancy

Limited human data available to inform drug-associated risk. For more information, contact the pregnancy exposure registry that monitors pregnancy outcomes in women exposed to anifrolumab at 1-877-693-9268.

Lactation

Not known whether anifrolumab is distributed into human milk; however, the drug has been detected in animal milk. Consider the benefits of breast-feeding, the potential for adverse effects from anifrolumab exposure to the breast-fed infant, and the mother’s clinical need for anifrolumab.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently from younger adult patients.

Hepatic Impairment

Based on pharmacokinetic analyses, baseline hepatic biomarkers (ALT and AST levels ≤2 times the ULN and total bilirubin) had no clinically relevant effects on anifrolumab clearance.

Renal Impairment

Based on pharmacokinetic analyses, clearance of anifrolumab similar between normal (eGFR >90 mL/minute/1.73 m²) and mild to moderate renal impairment (eGFR 30–89 mL/minute/1.73 m²).

Not evaluated in severe renal impairment or ESRD (eGFR <30 mL/minute/1.73 m²), but anifrolumab is not renally cleared.

Common Adverse Effects

Adverse drug reactions (incidence ≥5%): nasopharyngitis, upper respiratory tract infections, bronchitis, infusion-related reactions, herpes zoster, cough.

Drug Interactions

No formal drug interaction studies have been conducted.

Specific Drugs

Drug	Interaction
ACE Inhibitors	Concentrations not meaningfully altered
Antimalarials	Concentrations not meaningfully altered
Corticosteroids	Concentrations not meaningfully altered
Immunosuppressants (e.g., azathioprine, methotrexate, mycophenolate mofetil, mycophenolic acid, mizoribine)	Concentrations not meaningfully altered
NSAIAs	Concentrations not meaningfully altered
Statins	Concentrations not meaningfully altered

Anifrolumab Pharmacokinetics

Absorption

Bioavailability

Anifrolumab exhibits non-linear pharmacokinetics in healthy individuals over a dosage range of 100–1000 mg.

Following a dosage of 300 mg IV infusion every 4 weeks, steady-state attained by day 85.

Distribution

Extent

Likely present in human milk.

Elimination

Elimination Route

Exhibits non-linear type I interferon receptor (IFNAR1)-mediated clearance.

Not expected to undergo renal or hepatic elimination.

Half-life

Following infusion withdrawal after a 52-week treatment period, plasma levels of type I inducible genes return to baseline levels after 8–12 weeks.

Special Populations

No clinically meaningful differences in clearance based on age, race, ethnicity, region, gender, IFN status, or body weight.

Stability

Storage

Parenteral

Concentrate for Injection

Store between 2–8°C in the original carton to protect from light; do not freeze or shake.

Use the diluted solution immediately after preparation. If not used immediately, store the diluted solution between 2–8°C for no longer than 24 hours, or between 15–25°C for no longer than 4 hours. Protect from light; do not freeze the diluted solution.

Actions

Human IgG1κ monoclonal antibody produced in mouse myeloma cells by recombinant DNA technology; antagonist of the type I interferon receptor (IFNAR) that binds to subunit 1.
This antagonistic activity reduces the levels of surface IFNAR1 available for receptor assembly and prevents type I interferon (IFN) signaling, thereby blocking the activity of type I IFNs involved in responsive gene expression and downstream inflammatory and immunological processes.
Blockade of type 1 IFN also prevents plasma cell differentiation and normalizes subsets of peripheral T-cells.
Type I IFN inducible genes are involved in the pathogenesis of systemic lupus erythematosus (SLE) and are elevated in approximately 60-80% of adult patients with active disease.

Advice to Patients

Inform patients that anifrolumab may decrease their ability to fight infections, and that serious and fatal infections have occurred in patients receiving anifrolumab in clinical trials. Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment with anifrolumab. Advise patients to contact their healthcare provider if they develop any signs or symptoms of infection, which may include fever or flu-like symptoms, muscle aches, cough, shortness of breath, frequent urination or burning during urination, diarrhea or stomach pain, or shingles (a red skin rash that can cause pain and burning).
Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who received anifrolumab. Instruct patients to immediately report symptoms of an allergic reaction (e.g., anaphylaxis) such as swelling of the face, tongue, or mouth, breathing difficulties, dizziness, fainting, and/or lightheadedness to their healthcare provider.
Inform patients that they should not receive live or live-attenuated vaccines while receiving anifrolumab.
Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant, or become pregnant while receiving anifrolumab.
Inform women who are breast-feeding that anifrolumab may be present in breast milk.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Anifrolumab is available only from designated specialty pharmacies. Additional information is available at: [Web].